The identification of genetic associations with apoE alleles and Alzheimer's disease (AD) has profoundly influenced the way in which this disorder is conceived. In the CNS, "apoE's major defined function involves its binding to the LRP receptor." This multifunctional receptor is a large membrane bound receptor which is also a receptor for many proteins which are plaque components including a2-M, lactoferrin, and apoE. In this application, the hypothesis that genetic variability in the LRP receptor (and thus, in the efficacy of ligand binding and removal from the extracellular) contributes to the etiology of AD will be tested.